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Int. J. Mol. Sci. 2018, 19(6), 1742; https://doi.org/10.3390/ijms19061742

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

1
Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
2
Department of Dentistry, Graduate School, Kyung Hee University, Seoul 02447, Korea
3
Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
4
Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 25 April 2018 / Revised: 14 May 2018 / Accepted: 21 May 2018 / Published: 12 June 2018
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Abstract

The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (SASP) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway. View Full-Text
Keywords: melatonin; senescence; human periodontal ligament cells; cementoblasts; osteoclast differentiation; PIN1 melatonin; senescence; human periodontal ligament cells; cementoblasts; osteoclast differentiation; PIN1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Bae, W.-J.; Park, J.S.; Kang, S.-K.; Kwon, I.-K.; Kim, E.-C. Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts. Int. J. Mol. Sci. 2018, 19, 1742.

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